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Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology
Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,95...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810832/ https://www.ncbi.nlm.nih.gov/pubmed/35110524 http://dx.doi.org/10.1038/s41467-022-28167-1 |
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| author | Bjornsdottir, Gyda Stefansdottir, Lilja Thorleifsson, Gudmar Sulem, Patrick Norland, Kristjan Ferkingstad, Egil Oddsson, Asmundur Zink, Florian Lund, Sigrun H. Nawaz, Muhammad S. Bragi Walters, G. Skuladottir, Astros Th. Gudjonsson, Sigurjon A. Einarsson, Gudmundur Halldorsson, Gisli H. Bjarnadottir, Valgerdur Sveinbjornsson, Gardar Helgadottir, Anna Styrkarsdottir, Unnur Gudmundsson, Larus J. Pedersen, Ole B. Hansen, Thomas Folkmann Werge, Thomas Banasik, Karina Troelsen, Anders Skou, Soren T. Thørner, Lise Wegner Erikstrup, Christian Nielsen, Kaspar Rene Mikkelsen, Susan Jonsdottir, Ingileif Bjornsson, Aron Olafsson, Ingvar H. Ulfarsson, Elfar Blondal, Josep Vikingsson, Arnor Brunak, Soren Ostrowski, Sisse R. Ullum, Henrik Thorsteinsdottir, Unnur Stefansson, Hreinn Gudbjartsson, Daniel F. Thorgeirsson, Thorgeir E. Stefansson, Kari |
| author_facet | Bjornsdottir, Gyda Stefansdottir, Lilja Thorleifsson, Gudmar Sulem, Patrick Norland, Kristjan Ferkingstad, Egil Oddsson, Asmundur Zink, Florian Lund, Sigrun H. Nawaz, Muhammad S. Bragi Walters, G. Skuladottir, Astros Th. Gudjonsson, Sigurjon A. Einarsson, Gudmundur Halldorsson, Gisli H. Bjarnadottir, Valgerdur Sveinbjornsson, Gardar Helgadottir, Anna Styrkarsdottir, Unnur Gudmundsson, Larus J. Pedersen, Ole B. Hansen, Thomas Folkmann Werge, Thomas Banasik, Karina Troelsen, Anders Skou, Soren T. Thørner, Lise Wegner Erikstrup, Christian Nielsen, Kaspar Rene Mikkelsen, Susan Jonsdottir, Ingileif Bjornsson, Aron Olafsson, Ingvar H. Ulfarsson, Elfar Blondal, Josep Vikingsson, Arnor Brunak, Soren Ostrowski, Sisse R. Ullum, Henrik Thorsteinsdottir, Unnur Stefansson, Hreinn Gudbjartsson, Daniel F. Thorgeirsson, Thorgeir E. Stefansson, Kari |
| author_sort | Bjornsdottir, Gyda |
| collection | PubMed |
| description | Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (OR(IDD) = 0.92, P = 1.6 × 10(−39); OR(dorsalgia) = 0.92, P = 7.2 × 10(−15)) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10(−11)); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes. |
| format | Online Article Text |
| id | pubmed-8810832 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-88108322022-02-10 Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology Bjornsdottir, Gyda Stefansdottir, Lilja Thorleifsson, Gudmar Sulem, Patrick Norland, Kristjan Ferkingstad, Egil Oddsson, Asmundur Zink, Florian Lund, Sigrun H. Nawaz, Muhammad S. Bragi Walters, G. Skuladottir, Astros Th. Gudjonsson, Sigurjon A. Einarsson, Gudmundur Halldorsson, Gisli H. Bjarnadottir, Valgerdur Sveinbjornsson, Gardar Helgadottir, Anna Styrkarsdottir, Unnur Gudmundsson, Larus J. Pedersen, Ole B. Hansen, Thomas Folkmann Werge, Thomas Banasik, Karina Troelsen, Anders Skou, Soren T. Thørner, Lise Wegner Erikstrup, Christian Nielsen, Kaspar Rene Mikkelsen, Susan Jonsdottir, Ingileif Bjornsson, Aron Olafsson, Ingvar H. Ulfarsson, Elfar Blondal, Josep Vikingsson, Arnor Brunak, Soren Ostrowski, Sisse R. Ullum, Henrik Thorsteinsdottir, Unnur Stefansson, Hreinn Gudbjartsson, Daniel F. Thorgeirsson, Thorgeir E. Stefansson, Kari Nat Commun Article Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (OR(IDD) = 0.92, P = 1.6 × 10(−39); OR(dorsalgia) = 0.92, P = 7.2 × 10(−15)) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10(−11)); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes. Nature Publishing Group UK 2022-02-02 /pmc/articles/PMC8810832/ /pubmed/35110524 http://dx.doi.org/10.1038/s41467-022-28167-1 Text en © The Author(s) 2022, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Bjornsdottir, Gyda Stefansdottir, Lilja Thorleifsson, Gudmar Sulem, Patrick Norland, Kristjan Ferkingstad, Egil Oddsson, Asmundur Zink, Florian Lund, Sigrun H. Nawaz, Muhammad S. Bragi Walters, G. Skuladottir, Astros Th. Gudjonsson, Sigurjon A. Einarsson, Gudmundur Halldorsson, Gisli H. Bjarnadottir, Valgerdur Sveinbjornsson, Gardar Helgadottir, Anna Styrkarsdottir, Unnur Gudmundsson, Larus J. Pedersen, Ole B. Hansen, Thomas Folkmann Werge, Thomas Banasik, Karina Troelsen, Anders Skou, Soren T. Thørner, Lise Wegner Erikstrup, Christian Nielsen, Kaspar Rene Mikkelsen, Susan Jonsdottir, Ingileif Bjornsson, Aron Olafsson, Ingvar H. Ulfarsson, Elfar Blondal, Josep Vikingsson, Arnor Brunak, Soren Ostrowski, Sisse R. Ullum, Henrik Thorsteinsdottir, Unnur Stefansson, Hreinn Gudbjartsson, Daniel F. Thorgeirsson, Thorgeir E. Stefansson, Kari Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| title | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| title_full | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| title_fullStr | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| title_full_unstemmed | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| title_short | Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| title_sort | rare slc13a1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810832/ https://www.ncbi.nlm.nih.gov/pubmed/35110524 http://dx.doi.org/10.1038/s41467-022-28167-1 |
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